Total synthesis ad biological evaluation of JBIR-23

JBIR-23的全合成及生物学评价

• 批准号: 2754544
• 金额: --
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2754544
• 关键词: Total; synthesis; ad; biological; evaluation

Human malignant pleural mesothelioma (MPM) is an aggressive (fatal) lung cancer which is always associated with asbestos exposure. Typically symptoms do not appear until 20-40 years after the original exposure, with life expectancy then 12-18 months. Given the widespread use of asbestos during the 20th century and this long latency period, it is no surprise that cases of MPM continue to rise. Therefore there is an urgent need to develop novel therapeutic approaches for the treatemnt of MPM.Thus the development of new therapeutic agents is crucial. Almost all drugs on the market - for any symptom - tend to have their origins in a natural product: that is something isolated from nature. Unfortunately there are no novel drugs in development specifically targeting mesothelioma. The principle reason for this was that until recently, there were no reported natural products to serve as a lead compound - a starting point for the drug discovery process.This changed in 2009, with the report of JBIR-23 and -24, two microbial metabolites isolated from Streptomyces sp. AK-AB27: the first natural products specifically to demonstrate cytotoxicity against four MPM cell lines, with modest IC50 values of 10-50 uM.The overall aim of the project s to investigate the first synthesis of JBIR-23; to confirm its structure is the one proposed upon its isolation; to prepare a library of analogues of JBIR-23; finally to conduct extensive biological studies on these compounds.

人类恶性胸膜间皮瘤(MPM)是一种侵袭性(致命性)肺癌，常与石棉接触有关。通常情况下，最初接触病毒20-40年后才会出现症状，预期寿命为12-18个月。考虑到石棉在20世纪和这段漫长的潜伏期内的广泛使用，MPM病例继续上升也就不足为奇了。因此，迫切需要开发新的治疗方法来治疗MPM。因此，开发新的治疗药物至关重要。市场上几乎所有的药物--任何症状--往往都源于一种天然产品：这是一种与自然隔绝的东西。不幸的是，目前还没有专门针对间皮瘤的新药在开发中。其主要原因是，直到最近，还没有天然产物作为先导化合物的报道，这是药物发现过程的起点。这种情况在2009年发生了变化，从链霉菌中分离出的两种微生物代谢物JBIR-23和JBIR-24的报告。AK-AB27：第一个对四种MPM细胞具有细胞毒性的天然产物，IC50值为10-50微米。S项目的总体目标是研究JBIR-23的首次合成；确认其结构就是在其分离后提出的结构；建立JBIR-23的类似物文库；最后对这些化合物进行广泛的生物学研究。